Regulation of Isomerohydrolase Activity in the Visual Cycle
Abstract
While the overall biosynthetic pathway leading from all-trans-retinoids to 11-cis-retinoids in the visual cycle is understood, little is known about which step(s) may be rate-limiting and how control is exerted. One possible target for control is the isomerohydrolase, which processes all-trans-retinyl esters into 11-cis-retinol. The basal rate of 11-cis-retinol synthesis from all-trans-retinyl esters is extremely slow using bovine retinal pigment epithelial membranes [3.5 pmol of 11-cis-retinol min-1 (mg of protein)-1], and only small amounts of 11-cis-retinyl ester are formed. However, the addition of retinol binding proteins stimulates 11-cis-retinol formation by a factor of approximately 13. Specific protein-protein interactions are probably unimportant because bovine serum albumin and the physiologically relevant cellular retinaldehyde binding protein (CRALBP) both stimulate 11-cis-retinol formation to the same extent, although CRALBP does so at much lower concentrations. The relatively rapid rate of isomerization in the presence of binding proteins [44.3 pmol of 11-cis-retinol min-1 (mg of protein)-1] suggests that the rate-limiting enzyme in the visual cycle need not be the isomerohydrolase. Also, 11-cis-retinol is shown to inhibit isomerohydrolase, providing a simple mechanism for regulation of the visual cycle and the stimulating effect of binding proteins.
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CRALBP binds 11-cis-retinol, preventing unwanted isomerisation to all-trans-retinol and further esterification to retinyl esters.
“11-cis-retinol is then bound by a cellular retinaldehyde-binding protein (CRALBP), which prevents unwanted isomerisation to all-trans-retinol and further esterification to retinyl esters.”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [49]
CRALBP facilitates oxidation of 11-cis-retinol to 11-cis-retinal by 11-cis-retinol dehydrogenases RDH5 and RDH11.
“CRALBP also facilitates oxidation of 11-cis-retinol to 11-cis-retinal, the molecule in visual transduction, by 11-cis-retinol dehydrogenases, 11-cis-retinol dehydrogenase 5 (RDH5) and 11-cis-retinol dehydrogenase 11 (RDH11) [47,48,49].”
From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [49]
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- Authors
- Winston, A., & Rando, R. R.
- Affiliations
- Harvard University (US)
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1998-02-01
- Volume
- 37
- Issue
- 7
- Pages
- 2044-2050
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W1968242979
- Cited by
- 97
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 2 · 2020: 3 · 2018: 1 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 2 · 2012: 1
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (EY-04096)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Keywords
- visual cycle, retinol-binding protein, CRALBP, bovine serum albumin, enzyme regulation, product inhibition, retinal pigment epithelium, rate-determining step, protein-protein interaction
- MeSH terms
- Retinoid Isomerohydrolase, Animals, Carrier Proteins, Cattle, Cell Membrane, Enzyme Activation, Pigment Epithelium of Eye, Retinaldehyde, Serum Albumin, Bovine, Solubility, Time Factors, Vision, Ocular, cis-trans-Isomerases
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